Bone disorders, including those associated with primary or secondary bone cancer, traumatic injury to bone (e.g., fracture), aberrant osteolytic activity (e.g., bone metastases and wear-induced osteolysis), and osteoporosis, are a major health threat. Bones are constantly being remodeled through osteoclast and osteoblast activity. When there is an uncoupling between the cells, an imbalance between resorption and formation, or a traumatic event, bone quality and strength suffers.
Specifically, osteoporosis affects 44 million Americans, costing an estimated $19 billion in health expenditures in 2005. Osteoporosis is the result of elevated osteoclast activity and/or decreased osteoblast activity, which causes more bone to be resorbed than rebuilt. Bones become weaker and are more prone to fractures which can be fatal in older patients (National Osteoporosis Foundation). Orthoporotic fractures are common, with the incidence increasing with age, and are associated with considerable morbidity, mortality, and deterioration of the quality of life.
The underlying cause of osteoporosis is an imbalance in the rate of bone formation and resorption during skeletal remodeling due to the inability of osteoblasts to match the activity of osteoclasts. Most current osteoporosis therapies target osteoclasts and not osteoblasts. Thus, although these therapies slow bone resorption, they do not target bone anabolism, which represents a critical means to regenerate lost bone density. While there are interventions that reduce the risk of orthoporotic fractures, there is a lack of therapies that restore osteoblast function and initiate the replacement of already lost bone to restore bone health.
The ability to modulate bone formation and resorption is dependent on providing sustained and local delivery of existing or potential therapeutic agents. However, effective delivery of small molecules locally and sustainably to bone remains a significant challenge. For example, bolus delivery results in rapid loss of drug, resulting in little or no therapeutic efficacy. Further, local delivery of small molecules has not been successfully demonstrated in bone. Therefore, there is a need in the art for compositions and methods to provide local sustained delivery of therapeutic agents to promote bone formation. The present invention satisfies this unmet need.